Mass Spectrometry Reviews最新文献

{"title":"Evaluation of Common Posttranslational Modification Enrichment Strategies for Proteomics Analysis.","authors":"Yoonjung Lee","doi":"10.1002/mas.70046","DOIUrl":"https://doi.org/10.1002/mas.70046","url":null,"abstract":"<p><p>Posttranslational modifications (PTMs) play critical regulatory roles in cellular processes, and their dysregulation is implicated in numerous diseases and pathological conditions. Their importance to biological functions has spawned many efforts to accurately identify and quantify protein modifications using high-throughput methods, especially liquid chromatography tandem-mass spectrometry (LC-MS/MS). The typically low stoichiometry of PTMs in biological samples often necessitates enrichment strategies to achieve sufficient analytical sensitivity. However, the growing number and diversity of published enrichment methods have made it challenging to evaluate key methodological differences and their respective advantages. This review examines enrichment strategies for the major PTM classes: phosphorylation, acetylation, ubiquitination, SUMOylation, methylation, glycosylation, and ADP-ribosylation. Immunoaffinity-based, chromatographic, and chemical derivatization approaches are compared for each class in terms of their underlying principles and practical trade-offs. Based on published methods, the review considers enrichment specificity, coverage depth, sample input requirements, and workflow compatibility, with the aim of providing a consolidated reference to guide method selection and optimization for single- and multi-PTM profiling.</p>","PeriodicalId":206,"journal":{"name":"Mass Spectrometry Reviews","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mass Spectrometry Imaging-Guided Proteomics, an Emerging Frontier in Spatial Biology.","authors":"Kenneth Weke, Julian J Lum, David R Goodlett, Helena Pětrošová, Irena Dapic","doi":"10.1002/mas.70048","DOIUrl":"https://doi.org/10.1002/mas.70048","url":null,"abstract":"<p><p>Spatial heterogeneity is a defining feature of tissue organization, yet conventional proteomic analysis provides limited information about the spatial origins of identified proteins. Spatially guided proteomics addresses this limitation by using tissue imaging techniques to select regions of interest (ROIs) for localized analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Among the imaging modalities available for this purpose, mass spectrometry imaging (MSI) stands out for its ability to map diverse molecular species directly within tissue without predefined targets, allowing chemically distinct regions to guide tissue sampling. By bridging spatial molecular profiles with high protein coverage, MSI-guided proteomics offers comprehensive biological insight. This review examines the workflow from MSI data acquisition through ROI definition, image registration, tissue isolation, and sample preparation to LC-MS/MS analysis. We compare common MSI modalities, discuss methods for ROI isolation, and summarize advances in nanoproteomics methods that support analysis of tissue samples at the microscopic scale. We critically evaluate applications in cancer research, infectious disease, neuroscience, and environmental science. Finally, we discuss the challenges and future directions of MSI-guided proteomics. We conclude that ongoing developments in the MSI-guided proteomics workflow position it as an emerging strategy for investigating localized biological processes within heterogeneous tissues.</p>","PeriodicalId":206,"journal":{"name":"Mass Spectrometry Reviews","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149293532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative Top-Down Proteomics: A Review.","authors":"Kellye A Cupp-Sutton, Mai A Atallah, Zhitao Zhao, Samin Anjum, Trishika Chowdhury, Anju Teresa Sunny, Patrycja Szamweber, Si Wu","doi":"10.1002/mas.70051","DOIUrl":"https://doi.org/10.1002/mas.70051","url":null,"abstract":"<p><p>Top-down proteomics approaches have emerged as powerful strategies for investigating the effects of proteoform modifications, such as amino acid substitutions, truncation, and post-translational modifications (PTMs), on protein function and activity in biological systems. In addition to proteoform structure, proteoform abundance also influences cellular biochemistry by regulating signaling pathways and altering protein-protein interaction dynamics. Thus, accurate measurement of proteoform abundance is critical for examining cellular phenotypes and disease states. The application of quantitative proteomics strategies to top-down proteomics, however, has been challenging due to difficulties in extracting and solubilizing intact proteins, the wide dynamic range in proteoform abundance, limited sensitivity for low‑abundance species, and the need for advanced separations and robust deconvolution algorithms. Recent advances in top-down proteomics strategies, including methods to improve proteoform mass spectrometry data collection, sample preparation, and data analysis, have laid the groundwork for quantitative top-down proteomics. Here, we provide a comprehensive review of current quantitative top-down proteomics strategies and examine the applications, advantages, and challenges, including label-free, metabolic labeling, chemical tag labeling, and targeted quantification strategies.</p>","PeriodicalId":206,"journal":{"name":"Mass Spectrometry Reviews","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149284320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Keeping It Native: Non-Denaturing Approaches to Top-Down Protein Mass Spectrometry.","authors":"Michael Xiao, Edvaldo Vasconcelos Soares Maciel, Frederik Lermyte, Owen S Skinner","doi":"10.1002/mas.70050","DOIUrl":"https://doi.org/10.1002/mas.70050","url":null,"abstract":"<p><p>Top-down proteomics and top-down mass spectrometry approaches provide direct characterization of proteoforms; the specific molecular forms of proteins, including post-translational modifications, truncations, alternative splicing, and sequence variants. To date, most top-down studies have been performed under denaturing conditions, losing critical information about protein folding and noncovalent protein-protein and protein-ligand interactions. However, recent efforts to apply non-denaturing, or native, ionization to top-down mass spectrometry and top-down proteomics have shown substantial promise for characterizing these higher-order and more transient interactions. This review covers progress over the last 35 years in non-denaturing top-down approaches and addresses the inherent strengths and challenges of the technique. We cover three major areas of applications: (1) Ligand binding and drug discovery, (2) Structural biology, and (3) Proteomics aspects and bioinformatics.</p>","PeriodicalId":206,"journal":{"name":"Mass Spectrometry Reviews","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149260152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends in LC/GC-HRMS Non-Targeted Screening of Unknown Contaminants of Emerging Concern in Aquatic Systems: Workflows, No-Standard Identification, and Environmental Applications.","authors":"Gerald Enos Shija","doi":"10.1002/mas.70049","DOIUrl":"https://doi.org/10.1002/mas.70049","url":null,"abstract":"<p><p>Non-targeted screening (NTS) coupled with high-resolution mass spectrometry (HRMS) has revolutionized detection of unknown contaminants of emerging concern (CECs), including pharmaceutical transformation products, novel disinfection byproducts, emerging PFAS variants, and a wide diversity of other organic micropollutants, without reliance on reference standards. This critical review focuses on aquatic matrices (wastewater, surface water, drinking water, and related environmental waters) and examines current trends in LC-HRMS and GC-HRMS workflows, highlighting their complementarity for comprehensive chemical-space coverage in complex environmental matrices. Principal advances include generic sample preparation strategies, advanced data processing tools (MZmine, patRoon, Compound Discoverer), Schymanski et al.-based identification frameworks with recent harmonization efforts, and the integration of suspect-enhanced non-target approaches. Complementary LC/GC workflows, enhanced by ion mobility and multi-dimensional separations, significantly improve feature detection and identification confidence for unknowns. The review further explores the translation of NTS data into risk-assessment frameworks via effect-directed and virtual EDA approaches, as well as selected applications in wastewater-based epidemiology (WBE). Key challenges persist, including high data volume and complexity, false positives/negatives, matrix effects, semi-quantification uncertainty, and limited inter-laboratory reproducibility. Recent harmonization initiatives by the NORMAN network and interlaboratory studies are progressively addressing these gaps through standardized QA/QC and reporting practices. In conclusion, LC/GC-HRMS NTS offers transformative potential for early-risk detection and proactive regulatory decision-making, particularly in the context of expanding EPA PFAS monitoring. Future perspectives emphasize AI-driven automation, multi-omics integration, real-time monitoring platforms, and stronger linkage to policy frameworks. As harmonization and technological advances mature, NTS will shift environmental analysis from reactive targeted monitoring toward predictive, systems-level protection of human and ecological health.</p>","PeriodicalId":206,"journal":{"name":"Mass Spectrometry Reviews","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149260112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward Cadaveric Proteomics: A Theoretical Framework for Mass Spectrometry Analysis of Embalmed Human Tissues.","authors":"Lamar Nabil Nagshabandi, Sara Abdulmohsen AlHammadi, Hatouf Husni Sukkarieh, Osama Ezzeldin Abdelhadi, Ahmad Aljada","doi":"10.1002/mas.70047","DOIUrl":"https://doi.org/10.1002/mas.70047","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Mass spectrometry-based proteomics has been applied with considerable success to the analysis of formalin-fixed, paraffin-embedded (FFPE) tissues, and this success raises the question of whether the same methods can be applied to the embalmed human cadaveric specimens that are used in anatomical education and research. In this review, a theoretical framework is presented for the application of proteomic methods to embalmed cadaveric tissues, in which the feasibility of the approach is evaluated on the basis of the methods that have been established for FFPE tissue, and the critical gaps in the evidence are identified. Four questions are addressed: which of the methods that have been established for FFPE tissue can be transferred to embalmed tissue; how the post-mortem interval and the chemistry of the embalming fluid limit that transfer; which acquisition and quantification strategies are suited to proteins that carry a heavy burden of chemical modification; and which applications are already established in preserved human tissue and which of them still require validation in embalmed specimens. A comprehensive review of the literature was carried out on the proteomic methods for FFPE tissue, on the kinetics of post-mortem protein degradation, on the chemistry of embalming, and on the strategies for the reversal of crosslinks. Studies of post-mortem protein degradation place the critical threshold for embalming at 24 h if protein integrity is to be maintained; preservation is best when embalming takes place within 6-12 h. Embalming with formaldehyde produces extensive crosslinks between the proteins that are similar to those of the FFPE processing, and this suggests that the strategies for the reversal of the crosslinks that have been established for FFPE tissue may be compatible with embalmed tissue. The alternative methods of embalming, which include the ethanol-based and the salt-based approaches, may offer a better preservation of the proteins. However, the extended periods of preservation and the multi-component chemical environment of cadaveric embalming present challenges that exceed those of the clinical FFPE specimens. No published study has yet carried out a full proteomic analysis of an embalmed human cadaver. The rates of protein identification and the effectiveness of the processing remain theoretical projections that require experimental validation. Although the theoretical considerations suggest that the approach is feasible, there are significant gaps in the evidence between the established methods for FFPE tissue and the requirements of cadaveric specimens. The framework identifies the priority areas for experimental validation, which are the optimization of the reversal of the crosslinks, the assessment of the recovery of proteins with the different methods of embalming, and the development of specialized protocols for processing. The successful development of cadaveric proteomics could improve anatomical education through ","PeriodicalId":206,"journal":{"name":"Mass Spectrometry Reviews","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Rise of Top-Down Mass Spectrometry for the Characterization of Oligonucleotide Therapeutics","authors":"Molly S. Blevins,&nbsp;Christopher M. Crittenden,&nbsp;Bifan Chen","doi":"10.1002/mas.70037","DOIUrl":"10.1002/mas.70037","url":null,"abstract":"<div>\u0000 \u0000 <p>The therapeutic landscape has been rapidly expanding beyond traditional small molecules and biologics in recent years with the emergence of oligonucleotide therapeutics. As these oligonucleotide modalities grow in complexity and chemical modifications, conventional digestion-based mass spectrometry strategies start to yield redundant and ambiguous information. Alternatively, the top-down approach has the potential to provide a holistic view of therapeutic oligonucleotides. This review examines the rise of top-down mass spectrometry for the characterization of therapeutic oligonucleotides, with a focus on technological and methodological advances between 2020 and 2025. We cover sample preparation, sample introduction including separation, ionization, mass analysis, fragmentation approaches, data analysis strategies, and a discussion of long oligonucleotide and beyond for oligonucleotide top-down analysis. Finally, we provide a practical top-down workflow guidance on therapeutic oligonucleotides and conclude with a forward-looking perspective on the frontiers of the field.</p></div>","PeriodicalId":206,"journal":{"name":"Mass Spectrometry Reviews","volume":"45 6","pages":"1117-1139"},"PeriodicalIF":6.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148409809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The TriVersa NanoMate: Automation of Nano Electrospray Analyses","authors":"Simon Prosser,&nbsp;Gary Schultz,&nbsp;Thomas Corso,&nbsp;Daniel Eikel,&nbsp;Thomas Kurz,&nbsp;Jamey Jones,&nbsp;Jack Henion","doi":"10.1002/mas.70021","DOIUrl":"10.1002/mas.70021","url":null,"abstract":"<div>\u0000 \u0000 <p>The evolution of nano-electrospray ionization technology began in the mid-1980s. At that time, no commercial vendors supplied the requisite electrospray emitters, which featured internal diameters of just a few microns. Tips were manually fabricated by pulling heated glass capillaries to create micron and sub-micron inside diameter tips. High voltage was applied to a sample solution within the capillary body, and when placed close to a counter electrode of the atmospheric pressure ionization (API) mass spectrometer formed a sufficiently high electric field to produce an electrospray plume. Nano electrospray offered key advantages, including enhanced sensitivity and minimized matrix effects for chemical analysis due to better ionization efficiency and reduced contamination due to the lower mass transfer into the mass spectrometer orifice. By the late 1990s, Advion scientists utilized the Cornell Nanofabrication Facility equipment to create an array of nano-electrospray emitters etched in a silicon wafer. Key to the success of this planar emitter array was the inclusion of a dielectric layer that enabled the formation of an electric field estimated to be equivalent to that of a pulled glass capillary emitter with dimensions near one micron, but with a 28 micron outside diameter emitter. This “ESI Chip” was commercialized along with a robot named NanoMate to enable automated, reproducible, and robust nano electrospray of 96 consecutive samples from the chip-based array of micro-fabricated emitters. This paper explores the development and commercialization story of the NanoMate and its use to expand scientific knowledge in the field of protein non-covalent interactions, protein structure, lipidomics, drug metabolism, and a host of other applications.</p>\u0000 </div>","PeriodicalId":206,"journal":{"name":"Mass Spectrometry Reviews","volume":"45 6","pages":"1028-1039"},"PeriodicalIF":6.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146256891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Development of the Digital Ion Trap","authors":"Li Ding,&nbsp;Lulu Sun,&nbsp;Weimin Wang","doi":"10.1002/mas.70022","DOIUrl":"10.1002/mas.70022","url":null,"abstract":"<div>\u0000 \u0000 <p>The digital ion trap (DIT) is an ion trap in which the periodic trapping field is driven by digital signals—typically with a rectangular waveform—generated by fast-switching circuits. This paper reviews the research history of rectangular wave-driven quadrupole fields, as well as the invention and development of DITs. It summarizes studies on ion motion stability and secular frequency in both 3D and 2D configurations of DITs and discusses differences in the stability diagrams of DITs arising from different definitions of the <i>a</i> and <i>q</i> parameters. Additionally, this review outlines the performance advantages of the digital driving method in mass analysis and lists the novel analytical functions that have been realized using DIT technology. Finally, it presents the latest developments in commercial DIT instruments.</p>\u0000 </div>","PeriodicalId":206,"journal":{"name":"Mass Spectrometry Reviews","volume":"45 6","pages":"1040-1063"},"PeriodicalIF":6.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Rise of Trapped Ion Mobility Spectrometry: Principles, Applications, and Recent Developments","authors":"Erin M. Panczyk,&nbsp;Claudia Martelli,&nbsp;Mark E. Ridgeway,&nbsp;Mans Ekeloef,&nbsp;Daniel Hornburg,&nbsp;Benjamin J. Jones,&nbsp;Christopher A. Wootton,&nbsp;Matthew R. Lewis,&nbsp;Stuart Pengelley,&nbsp;Jean-Francois Greisch,&nbsp;Melvin A. Park","doi":"10.1002/mas.70034","DOIUrl":"10.1002/mas.70034","url":null,"abstract":"<div>\u0000 \u0000 <p>Trapped ion mobility spectrometry (TIMS) is a highly versatile alternative to the more conventional drift tube ion mobility spectrometer (DTIMS). In TIMS, ions are analyzed using an electric field that holds ions stationary against moving gas. In the basic TIMS, ions are accumulated and trapped in the electric field and then eluted over time according to their collision cross section (CCS) as the strength of the electric field is scanned down. The resultant small size and low operating voltage of TIMS compared to prior approaches make it ideal for hybridization with mass spectrometry. Since its introduction and coupling with Time-of-Flight Mass Spectrometry (TOFMS) in 2011, TIMS has been widely and successfully applied in various bioanalytical fields, including proteomics, glycomics, metabolomics, lipidomics, and native mass spectrometry. In particular, the first commercial TIMS-MS instrument introduced by Bruker Daltonics Inc. (timsTOF), launched in 2016, quickly shined as one of the main reference instruments in bottom-up proteomics. The increased peak capacity, resulting from the additional dimension of separation—that is, mobility—leads to mass spectra of reduced complexity and a greater depth of peptide identification. In this retrospective, different designs and operational modes of TIMS will be presented with a focus on the advantages, potentials and challenges of this technology within the fields of the omics sciences, spanning from metabolomics to structural biology, including single cell analysis. Additionally, the newest platforms utilizing TIMS technology will be introduced, with a focus on future applications and direction of the technology.</p>\u0000 </div>","PeriodicalId":206,"journal":{"name":"Mass Spectrometry Reviews","volume":"45 6","pages":"1087-1116"},"PeriodicalIF":6.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}